Abstract：
:Shprintzen-Goldberg syndrome (SGS) is characterized by severe marfanoid habitus, intellectual disability, camptodactyly, typical facial dysmorphism, and craniosynostosis. Using family-based exome sequencing, we identified a dominantly inherited heterozygous in-frame deletion in exon 1 of SKI. Direct sequencing of SKI further identified one overlapping heterozygous in-frame deletion and ten heterozygous missense mutations affecting recurrent residues in 18 of the 19 individuals screened for SGS; these individuals included one family affected by somatic mosaicism. All mutations were located in a restricted area of exon 1, within the R-SMAD binding domain of SKI. No mutation was found in a cohort of 11 individuals with other marfanoid-craniosynostosis phenotypes. The interaction between SKI and Smad2/3 and Smad 4 regulates TGF-β signaling, and the pattern of anomalies in Ski-deficient mice corresponds to the clinical manifestations of SGS. These findings define SGS as a member of the family of diseases associated with the TGF-β-signaling pathway.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Carmignac V,Thevenon J,Adès L,Callewaert B,Julia S,Thauvin-Robinet C,Gueneau L,Courcet JB,Lopez E,Holman K,Renard M,Plauchu H,Plessis G,De Backer J,Child A,Arno G,Duplomb L,Callier P,Aral B,Vabres P,Gigot N,Arbudoi
10.1016/j.ajhg.2012.10.002subject
Has Abstractpub_date
2012-11-02 00:00:00pages
950-7issue
5eissn
0002-9297issn
1537-6605pii
S0002-9297(12)00517-4journal_volume
91pub_type
杂志文章abstract：:The first 14 exons of the APC gene have been screened by the denaturation gradient gel electrophoresis method in 160 unrelated patients with familial adenomatous polyposis coli (APC) syndrome. Four polymorphic variants corresponding to silent mutations not associated with the disease phenotype were observed. Mutations...
journal_title：American journal of human genetics
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abstract：:Centromeric-mapping methods have been used to investigate the association between altered recombination and meiotic nondisjunction in humans. For trisomies, current methods are based on the genotypes from a trisomic offspring and both parents. Because it is sometimes difficult to obtain samples from both parents and b...
journal_title：American journal of human genetics
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abstract：:The opportunity raised by recombinant DNA technology to develop a linkage marker panel that spans the human genome requires cost-efficient strategies for its optimal utilization. Questions arise as to whether it is more cost-effective to convert a dimorphic restriction enzyme marker system into a highly polymorphic sy...
journal_title：American journal of human genetics
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doi：
更新日期：1986-07-01 00:00:00
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journal_title：American journal of human genetics
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abstract：:Pathogenetic mutations in mtDNA are found in the majority of patients with Leber hereditary optic neuropathy (LHON), and molecular genetic techniques to detect them are important for the diagnosis. A false-positive molecular genetic error has adverse consequences for the diagnosis of this maternally inherited disease....
journal_title：American journal of human genetics
pub_type： 杂志文章
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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更新日期：1978-01-01 00:00:00
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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doi：
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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doi：10.1086/381133
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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更新日期：1991-10-01 00:00:00
